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Poly(ethylene glycol) surface conjugated liposome encapsulated Hb (PEG-LEH) nanoparticles are considered a promising class of HBOC for use as a red blood cell (RBC) substitute. However, their widespread usage is limited by manufacturing processes which prevent material scale up. In this study, PEG-LEH nanoparticles were produced via a scalable and robust process using a high-pressure cell disruptor, and their biophysical properties were thoroughly characterized. Hb encapsulation, methemoglobin (metHb) level, O\n                    <jats:sub>2<\/jats:sub>\n                    -PEG-LEH equilibria, PEG-LEH gaseous (oxygen, carbon monoxide, nitric oxide) ligand binding\/release kinetics, lipocrit, and long-term storage stability allowed us to examine their potential suitability and efficacy as an RBC replacement. Our results demonstrate that PEG-LEH nanoparticle suspensions manufactured via a high-pressure cell disruptor have Hb concentrations comparable to whole blood (~12 g\/dL) and possess other desirable characteristics, which may permit their use as potential lifesaving O\n                    <jats:sub>2<\/jats:sub>\n                    therapeutics.\n                  <\/jats:p>","DOI":"10.1371\/journal.pone.0269939","type":"journal-article","created":{"date-parts":[[2022,7,8]],"date-time":"2022-07-08T14:07:33Z","timestamp":1657289253000},"page":"e0269939","update-policy":"https:\/\/doi.org\/10.1371\/journal.pone.corrections_policy","source":"Crossref","is-referenced-by-count":15,"title":["Scalable production and complete biophysical characterization of poly(ethylene glycol) surface conjugated liposome encapsulated hemoglobin (PEG-LEH)"],"prefix":"10.1371","volume":"17","author":[{"given":"Uddyalok","family":"Banerjee","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Savannah","family":"Wolfe","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1499-9620","authenticated-orcid":true,"given":"Quintin","family":"O\u2019Boyle","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8739-2155","authenticated-orcid":true,"given":"Clayton","family":"Cuddington","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3378-3772","authenticated-orcid":true,"given":"Andre F.","family":"Palmer","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"340","published-online":{"date-parts":[[2022,7,8]]},"reference":[{"issue":"2","key":"pone.0269939.ref001","doi-asserted-by":"crossref","first-page":"177","DOI":"10.1257\/jep.28.2.177","article-title":"The market for blood","volume":"28","author":"R. 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